Application of Next Generation Sequencing to Establish the Genetic Testing Platform for Thoracic Aortic Aneurysm and Dissection Syndrome

• Main Authors: Yu-Lin Fan Chiang, 范姜郁琳
• Other Authors: 楊偉勛
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/92030430283610040366

碩士 === 國立臺灣大學 === 分子醫學研究所 === 105 === Thoracic Aortic Aneurysm and Dissection syndrome (TAAD) can be divided into two main categories according to clinical features: (1) Syndromic, often accompanied by multiple groups of organ damage, including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), Ehlers-Danlos syndrome (EDS), Aneurysms-Osteoarthritis syndrome (AOS), and transforming growth factor-β signaling related diseases; (2) Non-syndromic, only in the aortic disease, generally divided into familial TAAD and sporadic TAAD. However, the diversity of clinical features or symptoms are not clear, and it not only resulting in the difficulties of clinical diagnosis, but also suffering greater pain to patients and their families. In this study, we enrolled patients from National Taiwan University Hospital "Cardiology Outpatient", "Pediatric Cardiology Outpatient" and "Department of Medical Genetics";30 patients with clinically diagnosed TAAD- Aneurysm/Dissection, and 19 patients with TAAD-non Aneurysm/Dissection but the clinical manifestations of suspected Marian syndrome (MFS) were included. We extracted gDNA from peripheral blood of these 49 patients, and detected 27 genes related to Syndromic TAAD and Non-syndromic TAAD by next-generation sequencing (NGS). Total detection rate was 49.0% (24/49), with 63.3% (19/30) for 30 TAAD- Aneurysm/Dissection diagnosed patients, and 26.3% (5/19) for 19 TAAD-non Aneurysm/Dissection cases. The accuracy rate was 100% (20/20) for the doubling check with Sanger sequencing. According to the ACMG (American College of Medical Genetics and Genomics) guidelines, we found 8 variants on FBN1 and 1 variant on FBN2 to be pathogenic or likely pathogenic, and they were genetic variants which not yet been reported so far. Comparing with traditional sequencing methods, NGS is a combination of micro-technologies to do millions of DNA sequencing simultaneously; it generates high throughputs with high resolution within several days, which help us to save time and money. With this method, we can help patients to find out their causes of thoracic aorta. Furthermore, the understanding of genetic composition of Taiwan patients expands our understanding of this disease.